Over 5 million people suffer from heart failure (HF) and 250,000 die annually, despite new medications and devices. Uniting strengths from diverse HF sites through the NHLBI, the National Heart Failure Network is vital to accelerate conceptual HF research and apply it to improve quality and length of life with HF. This proposal from Partners Heart Failure Program demonstrates dedication and expertise for improving HF outcomes, centered in HF clinics of Brigham and Women's and Massachusetts General Hospitals, enhanced by established collaboration with the Chabert HF site enrolling rural indigent patients in Louisiana. This represents 800 new patients and 5100 visits annually and 330 trial subjects the past 2 years. Expanded circles include 4 other Boston HF sites, 6 other Louisiana sites, and Partners Research and Education Program (PREP) supporting office-based clinical trials for 25 Boston community physicians. Objectives are: 1*) Facilitate establishment of an effective national network for research to improve outcomes in heart failure;with Two Major Aims: To contribute strong, diverse subject enrollment and to facilitate HF protocol design. Project A offers a template to assess the impact of regenerative therapy for late-stage HF, using catheter transfection of adeno-associated virus/SERCA2a protein. Project B provides a template for a 3-way trial of acute therapy in decompensated HF, comparing hormonal and mechanical to diuretic strategies for the cardiorenal syndrome. We advocate also the creation of two Vital Network Assets: a Parallel Advanced Registry to compare with VAD patients as the first Parallel Cohort analysis, and a Heart Failure DNA /Tissue Repository. 2*) Create the supportive matrix of senior, emerging, and junior investigators, with Training Core focus on rigorous didactics and diverse hands-on experiences to nurture the next generation of investigators. 3*) Enhance dissemination of network progress into community channels. Major strengths of this proposal are 1) breadth of expertise in clinical HF and relevant basic science;2) enhanced value from institutional commitments to infrastructure at 3 sites and PREP;3) real-time patient profiles for proven urban and rural enrollment;4) focus on assessing strategies in advanced HF;5) innovation into gene-based therapy for myocardial regeneration;and 6) successful precedent of inclusive collaboration for regional HF care and education and national NHLBI initiatives such as REMATCH, ESCAPE, and the National VAD Registry. (End of Abstract)